糖皮质激素受体的分子生物学特征及其在内耳的研究进展

糖皮质激素（glucocorticoid,GC）已广泛应用于自身免疫性内耳病、突发性聋、梅尼埃病等内耳疾病的治疗。在细胞水平GC与其受体结合,激活的受体转移至细胞核内调节基因的表达从而在靶器官发挥生物学效应。     

P2嘌呤受体在内耳中的分布特性和功能

在听觉系统中，外源性三磷酸腺苷(ATP)除作为耳蜗活性物质外，还可作为神经递质或调质，参与Corti器内感觉毛细胞及支持细胞的各种生理功能，从而产生一系列效应，调节耳蜗听觉生理功能；ATP的这种作用主要是通过P2嘌呤受体介导的信号传导完成的，现就P2嘌呤受体在内耳的分布特点及介导的信号传导在耳蜗听功能中的生物学作用作一综述。     

利钠尿肽在鼠内耳的表达及其意义

利钠尿肽(natriuretic peptides，NPs)是主要由心房、心室肌及血管内皮细胞分泌的一类具有强烈利尿、利钠、扩血管及降低血压等作用的多肽激素，在人体中枢和外周的水盐平衡代谢方面起重要的作用。它不仅存在于心血管中，在胆囊、睫状体、脑脉络丛等组织中也广泛存在。多年来，人们一直致力于将利钠尿肽用于与水盐代谢紊乱有关的疾病的治疗，并进行了积极的尝试，如将心房利钠多肽(心钠素)用于急性心力衰竭和慢性心力衰竭急性恶变期患者的治疗。本文就十余年来有关该类激素的生物学结构及功能、在鼠内耳的表达、对内耳血流量、声信号传导、水盐平衡调节的作用等方面的研究进展进行综述。     

Hormone receptors in the inner ear

Vasopressin binding sites could be clearly demonstrated in the cochlea. Membrane staining was mainly limited to the apical and ciliar membranes of the cochlear and vestibular hair cells, and hence to membranes in which adenylate cyclase activity could not be demonstrated. In addition to V2-vasopressin receptors that mediate hormonal signals by adenylate cyclase activation and cAMP release, in V1-vasopressin-receptors extracellular vasopressin signal is mediated by the breakdown of inositol phosphates and the release of inositol-triphosphates and diacylglycerol. Inositol triphosphates were found to be responsible for the intracellular mobilization of calcium. The localization of vasopressin binding sites at the hair cell membranes, therefore, suggests that vasopressin contributes to the breakdown and release of phospholipid messenger molecules and is thus probably involved in cochlear and vestibular signal transduction.     

Alpha and beta subunits of acetylcholine receptors in the human inner ear

The localization and distribution of nicotinic acetylcholine receptors (n-ACh-r) was characterized by studying alpha and beta subunits in the adult human inner ear by FITC fluorescence technique. In the cochlea, distinct fluorescence staining occurred for beta subunits in outer hair cells (OHCs), but no alpha subunits were identified. Beta subunits differ quantitatively between the three rows of OHCs, decreasing along a base-to-apex gradient in the cochlea. Both alpha and beta subunits were identified on spiral ganglion cells, adjacent nerve fibres and in vestibular hair cells (HCs). It would appear that they form an active complex in n-ACh-r at these locations.     

Inner ear autoantibodies and their targets in patients with autoimmune inner ear diseases

Immunological mechanisms are thought to play an important role in the pathogenesis of some cochleo-vestibular diseases. This study attempts to present further evidence of autoantibodies reactive against guinea pig inner ear proteins found in patients with autoimmune inner ear diseases (AIED) and specifically identifies the main target antigens of these antibodies. Sera from 110 patients with a clinical diagnosis of either rapidly progressive sensorineural hearing loss (n = 32). Ménière's disease (n = 41), sudden deafness (n = 6) or other aetiologies of hearing loss (n = 11) were screened by the Western blot technique. Forty-four percent of the patients' sera had antibodies to several inner ear proteins, of which the 30, 42 and 68 kDa proteins were found to be the most reactive. These highly reactive proteins were identified by gas-phase micro sequencing after digestion with trypsin and separation of peptide fragments by high-performance liquid chromatography. A partial sequence of each protein was determined. These data, together with those obtained from 2-dimensional gel electrophoresis followed by Western blotting, demonstrated that the 30 and 42 kDa inner ear proteins are the major peripheral myelin protein P0 and the beta-actin protein, respectively, while sequence analysis indicated that the 68 kDa protein is novel. These findings further support the hypothesis that several populations of antibodies may contribute to the enhanced immunological activity of AIED patients. They also add a new dimension to our knowledge of AIED and may open new avenues in the development of simple serological assays, which are easier to perform and more rapid than Western blotting.     

Estrogen receptors in the normal adult and developing human inner ear and in Turner's syndrome

The influence of estrogens, the female sex hormone, on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The presence of estrogen receptors alpha and beta has earlier been shown in the inner ear of mice and rats. The aim of this study was to map possible estrogen receptors in the human inner ear. Inner ear tissue from human adults, aborted human normal fetuses and fetuses with Turner's syndrome were collected. Paraffin embedded sections of adult and fetal inner ears were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptor alpha containing cells were found in the adult human inner ear only in the spiral ganglion, and estrogen receptor beta in the stria vascularis solely. The human fetal inner ear tissue from both normal and Turner fetuses showed a very weak staining of estrogen receptor alpha in the spiral ganglion cells, but no specific labeling of the K?lliker's organ of Corti at 13, 14 and 18 weeks of age. No staining of estrogen receptor beta was seen in the fetal inner ear.